1. Field of the Invention
It has long been known that salicylic acid has an anti-inflammatory activity. In anthranilic acid derivatives which have also an amino group of a high electron density at the ortho-position, it has been confirmed that N-phenyl-substituted products, i.e., meferamic acid and flufenamic acid, have an especially high anti-inflammatory activity. Most of these anthranilic acid derivatives having an anti-inflammatory activity have a monoaromatic ring as the N-substituent, and very few of them have any other N-substituent.
This invention relates to N-naphthyl-anthranilic acids having a naphthalene ring as the N-substituent and a process for the synthesis thereof. We have now arrived at N-naphthyl-anthranilic acid derivatives having especially interesting biological activities.
Although reports of N-naphthyl-anthranilic acids are known, the number of such reports is much smaller than the number of reports on N-phenyl-anthranilic acids. Further, most reports on N-naphthyl-anthranilic acids treat them as intermediates leading to benzacrizines. N-(substituted-naphthyl-1)anthranilic acids of this invention are novel compounds, and it has not been known that these compounds can be effectively used as medicines such as anti-inflammatory agents and analgesics.
2. Description of the Prior Art
These N-aryl-anthranilic acids are synthesized by several methods, and the most general method is one utilizing the Ullmann reaction. This Ullman reaction includes two types, one comprising condensing an aromatic amine with an o-halobenzoic acid in the presence of a copper catalyst, and the other comprising condensing a halogenated aromatic derivative with anthranilic acid in the presence of a copper catalyst. We tentatively refer to the former type as the normal Ullmann reaction and the latter type as the reverse Ullmann reaction. Most of methods for the synthesis of N-naphthylanthranilic acids, which have heretofore been reported in the literature, utilize the normal Ullmann reaction.
In connection with the intended products of this invention, we tried both methods, and it was confirmed that novel N-(substituted-naphtryl-1)anthranilic acids can be synthesized by both methods.
In Monatsh, 71, pages 122-127 (1937), W. Knap reports that when 1-bromo-2-methylnaphthalene and anthranilic acid were heated in the presence of copper powder and potassium carbonate in nitrobenzene (boiling at 210.degree. C.) to the boiling point of nitrobenzene, N-(2-methyl-1-naphthyl)-anthranilic acid was obtained in the form of a grayish yellow crystal having a melting point of 215.degree.-216.degree. C.
However, no disclosure is given in the above reference on pharmacological effects of the so-obtained N-(2-methyl-1-naphthyl) anthranilic acid, and no literature reference discloses any pharmacological effects of said compounds.